Cellular Heterogeneity and IL-17 Pathway Dynamics Reveal Insights into the Transition from Ulcerative Colitis to Colorectal Cancer Through scRNA-Seq Analysis.

INTRODUCTION

The progression of UC to CACRC involves substantial molecular and cellular alterations. A deeper understanding of these changes is essential for identifying potential therapeutic targets and improving disease outcomes.

METHODS

We performed scRNA-seq on tissue samples from a patient with coexisting UC and CACRC lesions, including normal colon, UC-affected tissue, and CACRC. Cell clustering, differential gene expression, and KEGG pathway enrichment analyses were conducted to characterize cellular heterogeneity and pathway dynamics.

RESULTS

Thirteen distinct cell clusters were identified, reflecting significant heterogeneity across disease stages. Six major cell types-B cells, T cells, epithelial cells, monocytes, neutrophils, and CMPs-were selected for in-depth analysis. Epithelial cells from UC samples showed marked upregulation of inflammatory genes such as IL-17A, CXCL1, IL-6, MMP3, and TNFAIP3, which were downregulated in CACRC. KEGG analysis revealed IL-17 signaling as a key pathway involved in disease progression. A progressive increase in Tregs, supported by elevated CD25 expression, was observed from normal tissue through UC to CACRC. Furthermore, C-MYC was significantly upregulated in CACRC epithelial cells, suggesting its role in tumor proliferation and metabolic reprogramming.

CONCLUSION

This study uncovers dynamic cellular and molecular changes during the transition from UC to CACRC, highlighting IL-17 signaling, Treg expansion, and C-MYC activation as potential drivers of malignancy and targets for future therapeutic intervention.